"Open the book to page ninety-nine and read, and the quality of the whole will be revealed to you."
--Ford Madox Ford

Saturday, November 28, 2009

Robert Marion’s "Genetic Rounds"

Robert Marion, M.D., is a professor of pediatrics and obstetrics and gynecology at the Albert Einstein College of Medicine in the Bronx, New York, is the director of clinical genetics at both the Montefiore Medical Center in the Bronx and Blythedale Children's Hospital, Valhalla, New York. He is the author of several published books, including the best-selling and timeless classics The Intern Blues and Learning to Play God: The Coming of Age of a Young Doctor.

An exploration of the human side of the Human Genome Project, Genetic Rounds is a series of essays about patients I’ve cared for during my career as a medical geneticist. Featuring medical detective work, scientific observation, and emotional encounters with patients and families, the essays are self-contained lessons, each expressing something I’ve learned from these encounters.

Page 99 is emblematic. The final page of “Relics,” which tells the story of the Kennedys, a couple who came to see me years after their only child, Sarah, had died of complications of spinal muscular atrophy (SMA), page 99 restates a theme of the essay. An inherited disorder in which nerves that control every muscle in the body inexplicably disappear, the child with SMA leads a nightmarish existence: normal at birth, they develop decreased muscle tone, a decreased ability to suck, and poor weight gain. The weakness progresses, eventually leading to paralysis of muscles involved in respiration. It’s the respiratory failure that’s lethal: most children die before reaching their first birthday.

Sarah Kennedy had lived this nightmare, dying at 10 months of age. Following her death, the Kennedys, understanding that each subsequent child would have a 25% chance of also being affected, had decided not to risk having more children. They came to see me however, because, through an accident, Mrs. Kennedy had become pregnant, and before terminating what was a much-wanted pregnancy, had been referred to find out if there was any way to diagnose SMA prenatally.

At that time, although the gene responsible for SMA had not been identified, its location on chromosome 5 had been determined. Through a technique called linkage, we could tell if the current fetus had inherited the non-working genes or not. But in order to do this, we needed DNA from Sarah. And unfortunately, DNA from the infant who’d died years before was simply not available.

It was not available, that is, until Mr. Kennedy mentioned in passing that the couple had kept relics of Sarah’s life: photographs, clothing, even her hairbrush. We realized that the brush contained the child’s hair, a potential source of DNA. Working with a lab that was able to extract that DNA, we discovered that the fetus, a boy whose DNA was obtained through an amniocentesis, was free of SMA. Instead of terminating the pregnancy, Mrs. Kennedy continued it, and six months after our first encounter, she gave birth to Sean, a perfectly formed baby whose nerves worked just fine.

Page 99 summarizes all this. The final paragraph reads:

It’s kind of ironic: in its early days, amniocentesis, in fact the entire field of medical genetics, was considered something of a search-and-destroy mission. Tests were performed…; abnormalities were identified; and since no treatment was available, couples were offered little choice but to either terminate the pregnancies or continue on, knowing that they were destined to deliver a baby with serious problems. But the reality of the situation has always been more like the story of the Kennedy family: without these genetic breakthroughs coupled with our ability to detect genetic disorders prenatally, couples with SMA and other inherited disorders would remain childless. The ability to test for the presence of SMA in Sean and his younger brother and sister allowed this family to have three children who otherwise would never have been born. This is one of the important reasons that, in spite of the sadness and angst associated with this field, we clinical geneticists continue to do what we do.